g-C3N4 is a promising material for hydrogen production from water via photo-catalysis, if we can tune its band gap to desirable levels. Using a combined experimental and ab initio approach, we uncover an almost perfectly linear relationship between the band gap and structural aspects of g-C3N4, which we show to originate in a changing overlap of wave functions associated with the lattice constants. This changing overlap, in turn, causes the unoccupied pz states to experience a significantly larger energy shift than any other occupied state (s, px, or py), resulting in this peculiar relationship. Our results explain and demonstrate the possibility to tune the band gap by structural means, and thus the frequency at which g-C3N4 absorbs light.
This paper explores the underlying mechanism through which ?-elemene inhibits the growth of intraocular melanoma in a mouse model. C57BL/6J mice were administered a subretinal injection of B16F10 melanoma cells and divided into two groups: treatment and control. The treatment group was administered ?-elemene through an intravitreal injection and the control group was injected with a blank emulsion. After 21 days of continuous treatment, tumor masses were removed and weighed. The mRNA expression levels of the urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-2, and MMP-9 were assayed by real-time PCR, and the protein expression levels of uPA, uPAR, MMP-2, and MMP-9 were assayed by immunocytochemistry and western blotting. Tumor size was inhibited by ?-elemene in the treatment group, and the expressions of uPA, uPAR, MMP-2, and MMP-9 were all downregulated at both the mRNA and the protein level compared with the control group. In a mouse model of intraocular melanoma, ?-elemene inhibits tumor growth by downregulating the expression of uPA, uPAR, MMP-2, and MMP-9.
Two novel acidothermophilic archaea, strain Ric-A(T) and Ric-F, were isolated from the muddy water samples of a sulfuric hot spring located at Tengchong County, Yunnan Province, China. They were aerobic and facultatively chemolithoautotrophic. Both strains could oxidize S(0) and K2S4O6 for autotrophic growth, and also could use organic materials for heterotrophic growth. Growth was observed at 55-75 °C and pH 1.5-6.5. The strains could oxidize metal sulfide ores, showing their potential in bioleaching. The DNA G+C content of Ric-A(T) and Ric-F were 41.8 and 41.6 mol%, respectively. Analysis of 16S rRNA gene sequences showed that the two strains share 99.8% sequence similarity to each other, but < 97% to the other known species of the genus Metallosphaera. DNA-DNA hybridization indicated that the isolates were different strains of a novel species of the genus Metallosphaera. Strains Ric-A(T) and Ric-F also shared a number of physiological and biochemical characteristics that distinguished them from the recognized species of the genus Metallosphaera. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons with their relatives, it was concluded that the strains Ric-A(T) and Ric-F represent a novel species of the genus Metallosphaera, for which the name Metallosphaera tengchongensis is proposed. The type strain is Ric-A(T) (=NBRC109472(T)=CGMCC1.12287(T)).
Graphitic overlayers on metals have commonly been considered as inhibitors for surface reactions due to their chemical inertness and physical blockage of surface active sites. In this work, however, we find that surface reactions, for instance, CO adsorption/desorption and CO oxidation, can take place on Pt(111) surface covered by monolayer graphene sheets. Surface science measurements combined with density functional calculations show that the graphene overlayer weakens the strong interaction between CO and Pt and, consequently, facilitates the CO oxidation with lower apparent activation energy. These results suggest that interfaces between graphitic overlayers and metal surfaces act as 2D confined nanoreactors, in which catalytic reactions are promoted. The finding contrasts with the conventional knowledge that graphitic carbon poisons a catalyst surface but opens up an avenue to enhance catalytic performance through coating of metal catalysts with controlled graphitic covers.
Objective. The relationship between the endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms and ankylosing spondylitis (AS) was inconsistent in the recent literatures, a meta-analysis was therefore performed. Methods. A total of 25 independent studies with 24,271 AS patients and 42,666 controls were included after searching electronic databases for studies published before June 2014. The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between ERAP1 polymorphisms and AS in different ethnicities. Results. This meta-analysis includes 25 studies that investigate 8 single nucleotide polymorphisms (SNPs; rs17482078, rs30187, rs2287987, rs27044, rs26653, rs10050860, rs27037, and rs27434) in ERAP1 gene. Overall, six SNPs were associated with AS; two SNPs (rs27044 and rs26653) were not when all studies were pooled into the meta-analysis (rs27044 G vs. C, OR = 1.058, 95% CI = 0.827-1.354; rs26653 C vs. G, OR = 1.154, 95% CI = 0.937-1.422). In Caucasians, all the 8 SNPs were significantly associated with AS. But 5 SNPs (rs17482078, rs2287987, rs27044, rs26653, and rs10050860) did not show statistical association with the risk of AS in Asians. Conclusion. ERAP1 polymorphisms were associated with AS in Caucasians, but their association with AS in Asians needs further exploration.
In advanced non-small cell lung cancer (NSCLC), the effectiveness of standard cytotoxic chemotherapy seems to have reached a 'plateau', and there is a continuous need for new treatments to further improve the prognosis. Cetuximab is a monoclonal antibody targeted at the epidermal growth factor receptor (EGFR) signalling pathway. Basically, it is designed to inhibit the growth and metastasis among other biological processes of cancer. In combination with chemotherapy, it has been evaluated as a first-line treatment for advanced NSCLC in some randomised controlled trials (RCTs), with inconsistent results.
A new synthesis route for preparing Dawson-type polyoxometalate (POM) based inorganic-organic hybrid materials is presented. Two new heteropolytungstate-based dimeric and oligomeric Pt(ii) acetylide inorganic-organic hybrid compounds (2PtOD and PPtOD) were prepared by Hagihara's dehydrohalogenating coupling of a terminal diacetylene POM hybrid containing diphosphoryl functionality and an appropriate platinum(ii) halide precursor. This method provides a rigid covalent linkage between the POM and the organometallic Pt(ii) acetylide moiety. The redox potential of the polyanion can be tuned by grafting the organic and organometallic groups on it. The photoelectric properties of hybrid LB films derived from these inorganic-organic composites were studied.
Context: Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. Objective: The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. Design: We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NSG mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing. Results: Mice carrying subcutaneous (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1?, and IL-6. Levels of HIF-1? and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3-22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo. Conclusion: To our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft.
The development of chemo-resistance may reduce the efficacy of chemotherapeutic drugs for treating hepatocellular carcinoma (HCC). Here, the effects of apigenin on intensifying the chemosensitivity of HCC cells and an HCC xenograft model in response to 5-fluorouracil (5-fu) were investigated. Sub-toxic doses of apigenin significantly enhanced the cytotoxicity of 5-fu in HCC cells. In vivo, the apigenin and 5-fu co-treatment group had a significant inhibitory effect on the growth of HCC xenograft tumors. To identify the tumor inhibitory effect of apigenin, we performed annexin V/PI dual staining assays, TUNEL assays and western blotting analyses to confirm the synergistic effects of apigenin and 5-fu on HCC apoptosis. Next, we found that co-incubation of apigenin with 5-fu increased the levels of reactive oxygen species (ROS) in HCC cells, which was followed by a decrease in the mitochondrial membrane potential (??m). In addition, co-treatment triggered the mitochondrial apoptotic pathway, as indicated by decreased Bcl-2 expression and loss of ??m, which significant activation of caspase-3 and PARP. Our study was the first to demonstrate that apigenin may potentiate the cytotoxicity of 5-fu in HCC via ROS-mediated drug resistance inhibition and concurrent activation of the mitochondrial pathways of apoptosis. This article is protected by copyright. All rights reserved.
An efficient cooperative biscinchona alkaloid and Lewis acid catalytic system was developed in the enantioselective ?-alkylation of 2-oxindoles with (3-indolyl)(phenyl)methanols to provide (2-oxindole)-linker-indole derivatives in good yields (70-83%) with high enantioselectivities (81%-92%).
The stabilities and electronic/band structures of single-layer bismuth oxyhalides have been investigated by employing first-principles calculations. The results indicate that the single-layer bismuth oxyhalide materials, except for BiOF, have robust energetic and dynamical stabilities because of their low formation energies and the absence of imaginary frequencies within the entire Brillouin zone. Furthermore, calculations of the electronic structures and optical absorptions indicate that single-layer BiOI possesses a favorable band gap, suitable band edge positions, different orbital characteristics and different effective masses at the valence band maximum (VBM) and conduction band minimum (CBM), thus presenting excellent photocatalytic activity for water splitting. Moreover, the resulting compressive strains can shift the band edge positions of the single-layer materials to more suitable places to enhance their photocatalytic activities.
Groundwater is the main source of water supply in China, and China's overall situation of groundwater pollution is not optimistic at present. Groundwater pollution risk evaluation and early-warning are the effective measures to prevent groundwater pollution. At present, research of groundwater early-warning method at home and abroad is still at the exploratory stage, and the sophisticated technology has not been developed for reference. This paper briefly described the data and technological demand of the early-warning method in different scales, and the main factors influencing the early-warning results of groundwater pollution were classified as protection performance of geological medium, characteristics of pollution sources, groundwater dynamics and groundwater value. Then the main early-warning indexes of groundwater pollution were screened to establish the early-warning model of regional or watershed scale by the index overlay method. At last, the established early-warning model was used in Baotou plain, and the different early-warning grades were zoned by the model. The research results could provide scientific support for the local management department to protect the groundwater resources.
Akebia saponin D (ASD) is a typical bioactive triterpenoid saponin obtained from the rhizome of Dipsacus asper Wall. Previous studies have found that ASD has a hepatoprotective effect in a mouse model. The purpose of this paper was to explore the molecular mechanism of the hepatoprotective effects of ASD on BRL cells and isolated rat liver mitochondria. We investigated the effects of ASD on rotenone-induced toxicity in BRL cells. The results showed that ASD inhibited the accumulation of reactive oxidant species, ATP deficiency, and mitochondrial membrane potential dissipation; ameliorates mitochondrial respiratory dysfunction, and improved the activity of complex I in a concentration-dependent manner, indicating that ASD likely improved mitochondrial function. ASD suppressed rotenone-induced BRL cell apoptosis and increased Bcl-2/Bax ratio. These results suggest that ASD may exert hepatoprotective effects against rotenone-induced toxicity through mitochondria. This study supports our previous research that ASD possesses hepatoprotective activity in vivo and it is worthy of further study.
The promising photovoltaic activity of pyrite (FeS2) is attributed to its excellent optical absorptivity and earth abundance, but its band gap, 0.95 eV, is slightly lower than the optimum value of 1.3 eV. Here we report the first investigation of strained FeS2, whose band gap can be increased by ?0.3 eV. The influence of uniaxial and biaxial strains on the atomic structure as well as the electronic and optical properties of bulk FeS2 is systematically examined by the first principles calculations. We found that the biaxial strain can effectively increase the band gap with respect to uniaxial strain. Our results indicate that the band gap increases with increasing tensile strain to its maximum value at 6% strain, but under the increasing compressive strain, the band gap decreases almost linearly. Moreover, the low intensity states at the bottom of the conduction band disappear and a sharp increase in the intensity appears at the lower energy level under the tensile strain, which causes the red shift of the absorption edge and enhances the overall optical absorption. With the increase of the band gap and enhanced optical absorption, FeS2 will make a better photovoltaic material.
Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77 %, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.
Abstract Polymerase chain reaction (PCR), long-and-accurate PCR and directly sequencing by primer walking was used to sequenced he complete mitochondrial genome sequence of Grumgzimailo's toad- headed agama, Phrynocephalus grumgrizimailoi. The Genbank accession was KM093859. There was 16,301?bp in length of the entire mitochondrial genome of P. grumgrizimailoi and the content of A, T, C, and G were 36.4%, 26.5%, 25.0% and 12.1%, respectively, that was similar to most vertebrate. The complete mitochondrial genome of P. grumgrizimailoi contain 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, plus 2 control regions and was similar to those of other Phrynocephalus sand lizards in gene arrangement and composition, except P. przewalskii and P. versicolor. The complete mitochondrial genome of P. grumgrizimailoi provided fundamental data for resolving phylogenetic relationship problems related to Agaimidae and genus Phrynocephalus.
Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q23 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1?) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1? and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN.
First-principles calculations are performed to investigate the adsorption of hydrogen onto Li-decorated hybrid boron nitride and graphene domains of (BN)(x)C(1-x) complexes with x = 1, 0.25, 0.5, 0.75, 0, and B0.125C0.875. The most stable adsorption sites for the nth hydrogen molecule in the lithium-decorated (BN)(x)C(1-x) complexes are systematically discussed. The most stable adsorption sites were affected by the charge localization, and the hydrogen molecules were favorably located above the C-C bonds beside the Li atom. The results show that the nitrogen atoms in the substrate planes could increase the hybridization between the 2p orbitals of Li and the orbitals of H2. The results revealed that the (BN)(x)C(1-x) complexes not only have good thermal stability but they also exhibit a high hydrogen storage of 8.7% because of their dehydrogenation ability.
The conventional strategy for cancer gene therapy offers limited control of specificity and efficacy. A possible way to overcome these limitations is to construct logic circuits. Here we present modular AND gate circuits based on CRISPR-Cas9 system. The circuits integrate cellular information from two promoters as inputs and activate the output gene only when both inputs are active in the tested cell lines. Using the luciferase reporter as the output gene, we show that the circuit specifically detects bladder cancer cells and significantly enhances luciferase expression in comparison to the human telomerase reverse transcriptase-renilla luciferase construct. We also test the modularity of the design by replacing the output with other cellular functional genes including hBAX, p21 and E-cadherin. The circuits effectively inhibit bladder cancer cell growth, induce apoptosis and decrease cell motility by regulating the corresponding gene. This approach provides a synthetic biology platform for targeting and controlling bladder cancer cells in vitro.
A homogeneous dispersion of hexagonal boron nitride nanosheets (BNNSs) in elastomers is obtained by solution compounding methods, and a high orientation of BNNSs is achieved by strong shearing. The composites show high thermal conductivities, especially when BNNS loading exceeds 17.5 vol%, indicating that the material is promising for thermal-management applications which need high thermal conductivity, low dielectric constant, and adequate softness.
A high-performance electrode for supercapacitors is designed and synthesized by growing electroactive NiCo2 O4 nanosheets on conductive Ni nanofoam. Because of the structural advantages, the as-prepared Ni@NiCo2 O4 hybrid nanostructure exhibits significantly improved electrochemical performance with high capacitance, excellent rate capability, and good cycling stability.
Three-dimensional (3D) hybrid layered materials receive a lot of attention because of their outstanding intrinsic properties and wide applications. In this work, the stability and electronic structure of three-dimensional graphene-MoS2 (3DGM) hybrid structures are examined based on first-principle calculations. The results reveal that the 3DGMs can easily self-assembled by graphene nanosheet and zigzag MoS2 nanoribbons, and they are thermodynamically stable at room temperature. Interestingly, the electronic structures of 3DGM are greatly related to the configuration of joint zone. The 3DGM with odd-layer thickness MoS2 nanoribbon is semiconductor with a small band gap of 0.01-0.25?eV, while the one with even-layer thickness MoS2 nanoribbon exhibits metallic feature. More importantly, the 3DGM with zigzag MoS2 nanoribbon not only own the large surface area and effectively avoid the aggregation between the different nanoribbons, but also can remarkably enhance Li adsorption interaction, thus the 3DGM have the great potential as high performance lithium ion battery cathodes.
Conserved clusters of genes encoding DsrE and TusA homologs occur in many archaeal and bacterial sulfur oxidizers. TusA has a well documented function as a sulfurtransferase in tRNA modification and molybdenum cofactor biosynthesis in Escherichia coli, and DsrE is an active site subunit of the DsrEFH complex that is essential for sulfur trafficking in the phototrophic sulfur-oxidizing Allochromatium vinosum. In the acidothermophilic sulfur (S(0))- and tetrathionate (S4O6(2-))-oxidizing Metallosphaera cuprina Ar-4, a dsrE3A-dsrE2B-tusA arrangement is situated immediately between genes encoding dihydrolipoamide dehydrogenase and a heterodisulfide reductase-like complex. In this study, the biochemical features and sulfur transferring abilities of the DsrE2B, DsrE3A, and TusA proteins were investigated. DsrE3A and TusA proved to react with tetrathionate but not with NaSH, glutathione persulfide, polysulfide, thiosulfate, or sulfite. The products were identified as protein-Cys-S-thiosulfonates. DsrE3A was also able to cleave the thiosulfate group from TusA-Cys(18)-S-thiosulfonate. DsrE2B did not react with any of the sulfur compounds tested. DsrE3A and TusA interacted physically with each other and formed a heterocomplex. The cysteine residue (Cys(18)) of TusA is crucial for this interaction. The single cysteine mutants DsrE3A-C(93)S and DsrE3A-C(101)S retained the ability to transfer the thiosulfonate group to TusA. TusA-C(18)S neither reacted with tetrathionate nor was it loaded with thiosulfate with DsrE3A-Cys-S-thiosulfonate as the donor. The transfer of thiosulfate, mediated by a DsrE-like protein and TusA, is unprecedented not only in M. cuprina but also in other sulfur-oxidizing prokaryotes. The results of this study provide new knowledge on oxidative microbial sulfur metabolism.
Toll-like receptor (TLR)-mediated signalling plays a role in cerebral ischaemia/reperfusion (I/R) injury. Modulation of TLRs has been reported to protect against cerebral I/R injury. This study examined whether modulation of TLR3 with poly (I:C) will induce protection against cerebral I/R injury. Mice were treated with or without Poly (I:C) (n = 8/group) 1 hr prior to cerebral ischaemia (60 min.) followed by reperfusion (24 hrs). Poly (I:C) pre-treatment significantly reduced the infarct volume by 57.2% compared with untreated I/R mice. Therapeutic administration of Poly (I:C), administered 30 min. after cerebral ischaemia, markedly decreased infarct volume by 34.9%. However, Poly (I:C)-induced protection was lost in TLR3 knockout mice. In poly (I:C)-treated mice, there was less neuronal damage in the hippocampus compared with untreated I/R mice. Poly (I:C) treatment induced IRF3 phosphorylation, but it inhibited NF-?B activation in the brain. Poly (I:C) also decreased I/R-induced apoptosis by attenuation of Fas/FasL-mediated apoptotic signalling. In addition, Poly (I:C) treatment decreased microglial cell caspase-3 activity. In vitro data showed that Poly (I:C) prevented hypoxia/reoxygenation (H/R)-induced interaction between Fas and FADD as well as caspase-3 and -8 activation in microglial cells. Importantly, Poly (I:C) treatment induced co-association between TLR3 and Fas. Our data suggest that Poly (I:C) decreases in cerebral I/R injury via TLR3 which associates with Fas, thereby preventing the interaction of Fas and FADD, as well as microglial cell caspase-3 and -8 activities. We conclude that TLR3 modulation by Poly (I:C) could be a potential approach for protection against ischaemic stroke.
Colorectal cancer (CRC) is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations (CNVs) of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China.
G protein-regulated cell function is crucial for cardiomyocytes, and any deregulation of its gene expression or protein modification can lead to pathological cardiac hypertrophy. Herein, we report that protein prenylation, a lipidic modification of G proteins that facilitates their association with the cell membrane, might control the process of cardiomyocyte hypertrophy. We found that geranylgeranyl diphosphate synthase (GGPPS), a key enzyme involved in protein prenylation, played a critical role in the postnatal heart growth through regulating the cardiomyocyte size. Cardiac-specific knockout of GGPPS in mice led to spontaneous cardiac hypertrophy beginning from 4(th) week, accompanied with the persistent enlargement of cardiomyocytes. This hypertrophic effect occurred by altered prenylation of G proteins. Evaluation of the prenylation, membrane association and hydrophobicity showed that Rheb was hyperactivated and increased mTORC1 signaling pathway after GGPPS deletion. Protein farnesylation or mTORC1 inhibition blocked GGPPS knockdown-induced mTORC1 activation and suppressed the larger neonatal rat ventricle myocyte size and cardiomyocyte hypertrophy in vivo, demonstrating a central role of FPP/Rheb/mTORC1 axis for GGPPS deficiency-induced cardiomyocyte hypertrophy. The sustained cardiomyocyte hypertrophy progressively provoked cardiac decompensation and dysfunction, ultimately causing heart failure and adult death. Importantly, GGPPS was downregulated in the hypertrophic hearts of mice subjected to transverse aortic constriction (TAC) and in the failing human hearts. Moreover, HPLC-MS/MS detection revealed that myocardial farnesyl diphosphate (FPP) to geranylgeranyl diphosphate (GGPP) ratio was enhanced after pressure overload. Our observations conclude that the alteration of protein prenylation promotes cardiomyocyte hypertrophic growth, which acts as a potential cause for pathogenesis of heart failure and may provide a new molecular target for hypertrophic heart disease clinical therapy.
Microbial attachment to drinking water pipe surfaces facilitates pathogen survival and deteriorates disinfection performance, directly threatening the safety of drinking water. Notwithstanding that the formation of biofilm has been studied for decades, the underlying mechanisms for the origins of microbial surface attachment in biofilm development in drinking water pipelines remain largely elusive. We combined experimental and mathematical methods to investigate the role of environmental stress-mediated cell motility on microbial surface attachment in chlorination-stressed drinking water distribution systems. Results show that at low levels of disinfectant (0.0-1.0 mg/L), the presence of chlorine promotes initiation of microbial surface attachment, while higher amounts of disinfectant (>1.0 mg/L) inhibit microbial attachment. The proposed mathematical model further demonstrates that chlorination stress (0.0-5.0 mg/L)-mediated microbial cell motility regulates the frequency of cell-wall collision and thereby controls initial microbial surface attachment. The results reveal that transport processes and decay patterns of chlorine in drinking water pipelines regulate microbial cell motility and, thus, control initial surface cell attachment. It provides a mechanistic understanding of microbial attachment shaped by environmental disinfection stress and leads to new insights into microbial safety protocols in water distribution systems.
We investigated the oncogenic role of SETDB1 focusing on non-small cell lung cancer (NSCLC) having high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry, 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p?0.0001). Percent positive cells and intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumor size in a murine xenograft model; while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT/?-catenin pathway and diminished P53 expression resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests therapeutic targeting SETDB1 may benefit patients whose tumors express high levels of SETDB1.
Studies investigating the association between matrix metalloproteinases (MMPs) gene polymorphisms and preeclampsia (PE) reported contradictory or non-conclusive results. We performed a meta-analysis of five studies that examined the relationship between PE and the MMP9-1562C>T polymorphism. The PubMed, Embase, and Google Scholar databases were searched to access the relevant genetic association studies up to September 2013. The meta-analysis revealed that there was no evidence for significant association between MMP9-1562C>T polymorphism and risk of PE. Large, multiethnic confirmatory, and well-designed studies are needed to further explore the relation between preeclampsia and polymorphisms of the MMPs gene.
The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
The Ad5/11 chimeric oncolytic adenovirus represents a promising new platform for anticancer therapy. Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells and is the most common malignant myeloid disorder in adults. Myeloid and other hematopoietic cell lineages are involved in the process of clonal proliferation and differentiation. In the present study, we aimed to ascertain whether chimeric oncolytic adenovirus-mediated transfer of the human interleukin-24 (IL-24) gene induces enhanced antitumor potency. Our results showed that the Ad5/11 chimeric oncolytic adenovirus carrying hIL-24 (AdCN205?11-IL-24) produced high levels of hIL-24 in AML cancer cells, as compared with the Ad5 oncolytic adenovirus expressing hIL-24 (AdCN205-IL-24). AdCN205-11-IL-24 specifically induced a cytotoxic effect on AML cancer cells, but had little or no effect on a normal cell line. AdCN205-11-IL-24 induced higher antitumor activity in AML cancer cells by inducing apoptosis in vitro. This study suggests that transfer of IL-24 by an Ad5/11 chimeric oncolytic adenovirus may be a potent antitumor approach for AML cancer therapy.
Laparoscopic appendectomy (LA) has been rapidly applied worldwide recently. The issue of surgical site infection (SSI) after appendectomy needs to be re-investigated and analyzed along with this trend. This study aimed to identify risk factors of SSI after appendectomy in recent years.
The present paper,on the basis of analyzing the terrain scattering characteristics, proposed a novel supervised classification method combined with complex Wishart classifier ideology. This method used coherent matrix which almost contains all the polarization information to make subsequent adjustments for the supervised classification result to achieve higher accuracy division categories. For the first beginning, supervised classification was carried out on the Cloude & Pottier polarimetric characteristics combination to get the initial classification result. Then, in order to achieve the purpose to correct the mistakes resulting from just using the spatial distribution of feature vectors in supervised classification, we did some analysis as follow. The accuracy analysis of the classification results and the analysis of study area feature scattering similarity play an important role in our study to help us make the determination that the pixels need to be adjusted. Furthermore, taking the mean value of each category coherence matrix as the initial cluster centers of subsequent iterations, and using Kernel Fuzzy C-Means algorithm to adjust the fixed pixel set categories by subsequent category iterative correction, the fine and high-accuracy classification results were obtained, combined with complex Wishart distribution of coherence matrix. The domestic X-band full polarization SAR data of Lingshui area in Hainan province was applied in this classification experiment. The experiment results demonstrate that the proposed method can obtain a favorable classification accuracy polarization SAR image classification results, and better meet the scattering characteristics of the surface objects compared to the original method.
Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.
Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague-Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 °C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 °C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.
Extraction of surface models of a hip joint from CT data is a pre-requisite step for computer assisted diagnosis and planning (CADP) of periacetabular osteotomy (PAO). Most of existing CADP systems are based on manual segmentation, which is time-consuming and hard to achieve reproducible results. In this paper, we present a Fully Automatic CT Segmentation (FACTS) approach to simultaneously extract both pelvic and femoral models. Our approach works by combining fast random forest (RF) regression based landmark detection, multi-atlas based segmentation, with articulated statistical shape model (aSSM) based fitting. The two fundamental contributions of our approach are: (1) an improved fast Gaussian transform (IFGT) is used within the RF regression framework for a fast and accurate landmark detection, which then allows for a fully automatic initialization of the multi-atlas based segmentation; and (2) aSSM based fitting is used to preserve hip joint structure and to avoid penetration between the pelvic and femoral models. Taking manual segmentation as the ground truth, we evaluated the present approach on 30 hip CT images (60 hips) with a 6-fold cross validation. When the present approach was compared to manual segmentation, a mean segmentation accuracy of 0.40, 0.36, and 0.36 mm was found for the pelvis, the left proximal femur, and the right proximal femur, respectively. When the models derived from both segmentations were used to compute the PAO diagnosis parameters, a difference of 2.0 ± 1.5°, 2.1 ± 1.6°, and 3.5 ± 2.3% were found for anteversion, inclination, and acetabular coverage, respectively. The achieved accuracy is regarded as clinically accurate enough for our target applications.
The effect of genetic markers associated with IgA nephropathy on risk of disease in sub-phenotype and progression is uncertain. Data from 2096 Chinese patients were used to create both un-weighted (uw) and weighted (w) genetic risk score (GRS). The association between GRS with disease susceptibility and clinical parameters were assessed. All nine selected single nucleotide polymorphisms (SNPs) were associated with susceptibility to IgAN. uwGRS and wGRS showed a similar fit in disease associations. With every 1-unit increase in the uwGRS, the disease risk increased by approximately 20%; whereas every one standard deviation increase in the wGRS, disease risk increased by approximately 40% ~ 60%. Association between rs3803800 and serum IgA was replicated, and risk groups in GRSs were associated with increased IgA/IgA1 levels. uwGRS9 ? 16 was an independent predictor for end stage renal disease (ESRD) in IgAN, with a relative risk of 2.52 (p = 6.68 × 10(-3)). In conclusion, we observed that GRSs comprising nine SNPs identified in a GWAS of IgAN were strongly associated with susceptibility to IgAN. The high risk GRS9 group had a high risk of ESRD in follow-up.
Co-stimulatory molecules play important roles in T cell-mediated immune response and transplantation. Numerous epidemiological studies have evaluated the association between CD28, CTLA-4 gene variant and allograft rejection. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CD28 IVS3 +17T/C variant, CTLA-4, CD86 and PDCD1 gene polymorphisms were associated with allograft rejection susceptibility. PubMed and Embase (before 2014-3-25), were searched for studies on the relationship of CD28, CTLA-4, CD86 and PDCD1 gene polymorphisms and the incidence of allograft rejection susceptibility. Eligible articles were included for data extraction. The main outcome was the frequency of co-stimulate molecule gene polymorphisms between rejection and non-rejection populations. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Significant associations of the CD28 IVS3 +17T/C variant with acute allograft rejection susceptibility were found (CC +CT/TT OR, 1.45; 95% CI, 1.08-1.94; P=0.01). Also we found an association of the CD28 IVS3 +17T/C variant with kidney allograft rejection cases (CC +CT/TT OR, 1.72; 95% CI, 1.19-2.49; P=0.004) and (C allele OR, 1.74; 95% CI, 1.11-2.75; P=0.02), but not established for liver allograft rejection cases (CC +CT/TT OR, 1.19; 95% CI, 0.47-2.98; P=0.72) and (C allele OR, 0.96; 95% CI, 0.67-1.39; P=0.84). And we found an association of the CD86 +1057G/A variant with non-allograft rejection cases (AA +AG/GG OR, 0.35; 95% CI, 0.14-0.85; P=0.02). This meta-analysis demonstrates that the CD28 IVS3 +17T/C variant might increase acute allograft rejection risk in kidney transplant but not in liver transplant, and there was an association between CD86 +1057G/A variant and reduced acute rejection risk. Further studies will be needed to confirm our findings.
Metallosphaera cuprina is able to grow either heterotrophically on organics or autotrophically on CO2 with reduced sulfur compounds as electron donor. These traits endowed the species desirable for application in biomining. In order to obtain a global overview of physiological adaptations on the proteome level, proteomes of cytoplasmic and membrane fractions from cells grown autotrophically on CO2 plus sulfur or heterotrophically on yeast extract were compared. 169 proteins were found to change their abundance depending on growth condition. The proteins with increased abundance under autotrophic growth displayed candidate enzymes/proteins of M. cuprina for fixing CO2 through the previously identified 3-hydroxypropionate/4-hydroxybutyrate cycle and for oxidizing elemental sulfur as energy source. The main enzymes/proteins involved in semi- and non-phosphorylating Entner-Doudoroff (ED) pathway and TCA cycle were less abundant under autotrophic growth. Also some transporter proteins and proteins of amino acid metabolism changed their abundances, suggesting pivotal roles for growth under the respective conditions.
Numerous studies have assessed the concentration-response (C-R) relationships between long-term exposure to particulate matter (PM) and mortality from cardiopulmonary diseases, but few studies have evaluated the C-R relationships between PM exposure and morbidity of chronic respiratory diseases or their symptoms, and to date no systematic review has been published on the characteristics of the C-R curves between PM exposure and respiratory disease morbidity. Screening of all available studies in Medline identified ten studies with figures or scatter plots showing the C-R relationships between PM exposure and chronic bronchitis or chronic cough/phlegm. The C-R relationships showed ballistic 'S' shaped curves, linear in the low to moderate PM range and flattening out in the high PM range. Moreover, the shape and level of the C-R curves differed markedly between susceptible and nonsusceptible populations. New evidence from a prospective cohort study confirmed that the C-R relationship between PM reduction and beneficial effects on respiratory health may be due to the decreased incidence of respiratory symptoms and increased recovery in individuals with symptoms of bronchitis. Additional studies are needed to assess the C-R relationships between different PM contents and chronic health parameters, especially in geographic areas with high PM pollution and in more susceptible populations. Evidence from prospective cohort studies in developing countries with areas of high PM pollution may help evaluate the burden of chronic respiratory disease attributable to PM pollution and air quality standards.
Fat distribution affects the risk of developing obesity-related chronic diseases. Glypican 4 (Gpc4) may be involved in the regulation of obesity and body fat distribution. The aim of the study was to explore whether Gpc4 affects fat accumulation and the possible mechanism. C57BL/6J mice were fed with a high-fat diet for eight weeks and treated with a peroxisome proliferators-activated receptor ? (PPAR?) agonist, rosiglitazone, for another four weeks. The weight of inguinal and epididymal fat pads was determined. The Gpc4 mRNA and protein expression and two probable regulators of the Gpc4 gene, specificity protein 1 (Sp1) and Sp3 mRNA, were also measured. Mice treated with rosiglitazone showed a significant increase in subcutaneous fat weight compared with the untreated mice. The expression of Gpc4 mRNA and protein was significantly higher in visceral than in subcutaneous fat in all the groups. Compared with untreated mice the expression of Gpc4 and Sp3 mRNA in subcutaneous fat and the expression of Sp1 and Sp3 mRNA in visceral fat in mice treated with rosiglitazone increased significantly. The Sp3/Sp1 ratio was consistent with the expression of Gpc4 mRNA and protein in subcutaneous and visceral fat. The present study indicated that Gpc4 may play an important role in fat distribution, and this effect is perhaps regulated by the ratio of Sp3/Sp1 in the subcutaneous and visceral fat tissues.
Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
There are no large series comparing the distally based perforator-plus sural fasciocutaneous flap used in pediatric and adult populations. The flaps were divided into two groups: the children (patient's age<14 years) group (n=53) and the adults (patient's age ? 18 years) group (n=148). We compared flap-viability-related complications and their potential risk factors. In the patients with at least 12-month postoperative follow-up, the reconstruction outcomes, donor-site morbidities, and transitory and permanent swelling of the affected lower limb were compared. Partial necrosis, marginal necrosis, and overall complication rates were 13.2, 3.8, and 17.0% in the pediatric group, and 12.2, 1.4, and 13.6% in the adult group, respectively; the differences were not statistically significant (p>0.05). Incidences of hypertrophic scar and pruritus at the donor site were significantly higher, while incidence of transitory swelling of the affected lower limb was significantly lower in the pediatric group. This flap in children is similar to that in adults in the reliability.
X-ray Photoelectron Spectroscopy (XPS) was used to characterize the nitrogen species in perfluorophenylazide (PFPA) self-assembled monolayers. PFPA chemistry is a novel immobilization method for tailoring the surface properties of materials. It is a simple route for the efficient immobilization of graphene, proteins, carbohydrates and synthetic polymers onto a variety of surfaces. Upon light irradiation, the azido group in PFPA is converted to a highly reactive singlet nitrene species that readily undergoes CH insertion and C=C addition reactions. Here, the challenge of characterizing the PFPA modified surfaces was addressed by detailed XPS experimental analyses. The three nitrogen peaks detected in the XPS N1s spectra were assigned to amine/amide (400.5 eV) and azide (402.1 and 405.6 eV) species. The observed 2:1 ratio of the areas from the 402.1 eV to 405.6 eV peaks suggests the assignment of the peak at 402.1 eV to the two outer nitrogen atoms in the azido group and assignment of the peak at 405.6 eV to the central nitrogen atom in the azido group. The azide decomposition as the function of x-ray exposure was also determined. Finally, XPS analyses were conducted on patterned graphene to investigate the covalent bond formation between the PFPA and graphene. This study provides strong evidence for the formation of covalent bonds during the PFPA photocoupling process.
The family of bulk metal phosphorus trichalcogenides (APX3, A = M(II), M(I)(0.5)M(III)(0.5); X = S, Se; M(I), M(II), and M(III) represent Group-I, Group-II, and Group-III metals, respectively) has attracted great attentions because such materials not only own magnetic and ferroelectric properties, but also exhibit excellent properties in hydrogen storage and lithium battery because of the layered structures. Many layered materials have been exfoliated into two-dimensional (2D) materials, and they show distinct electronic properties compared with their bulks. Here we present a systematical study of single-layer metal phosphorus trichalcogenides by density functional theory calculations. The results show that the single layer metal phosphorus trichalcogenides have very low formation energies, which indicates that the exfoliation of single layer APX3 should not be difficult. The family of single layer metal phosphorus trichalcogenides exhibits a large range of band gaps from 1.77 to 3.94 eV, and the electronic structures are greatly affected by the metal or the chalcogenide atoms. The calculated band edges of metal phosphorus trichalcogenides further reveal that single-layer ZnPSe3, CdPSe3, Ag0.5Sc0.5PSe3, and Ag0.5In0.5PX3 (X = S and Se) have both suitable band gaps for visible-light driving and sufficient over-potentials for water splitting. More fascinatingly, single-layer Ag0.5Sc0.5PSe3 is a direct band gap semiconductor, and the calculated optical absorption further convinces that such materials own outstanding properties for light absorption. Such results demonstrate that the single layer metal phosphorus trichalcogenides own high stability, versatile electronic properties, and high optical absorption, thus such materials have great chances to be high efficient photocatalysts for water-splitting.
Matrix metalloproteinase 9 (MMP-9) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. The possible prognostic value of MMP-9 in osteosarcoma has also been examined, but due to inconsistent results between studies, it has not been possible to draw firm conclusions. To clarify this issue, we conducted a meta-analysis of published studies to provide a comprehensive evaluation of the effect of high MMP-9 expression on the survival outcomes of osteosarcoma patients. Seven studies with a total of 339 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to evaluate the effect of MMP-9 expression on overall survival. Meta-analysis showed that patients with high MMP-9 expression were significantly associated with lower overall survival when compared to their counterparts with low or undetectable MMP-9 expression (OR=6.13, 95 % CI 3.45-10.89, P<0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. The results from the systematic review and meta-analysis show that MMP-9 is an effective biomarker for predicting survival of patients with osteosarcoma.
Neutropenia is a life-threatening side effect of irinotecan, and uridine diphosphate glucuronosyltransferases (UGTs) gene polymorphisms are considered to be one of the predictive markers of irinotecan-related toxicities. Many studies have demonstrated that patients bearing UGT1A1*28 have a higher risk of severe neutropenia on toxicity of irinotecan. However, UGT1A1 (TA7/TA7) was very rare in Asian populations. Some researches reported that UGT1A1*28 and/or UGT1A1*6 could predict irinotecan-induced toxicities in Asian populations, but controversial conclusions still remained. This study aims to investigate the association between UGT1A1 gene polymorphisms *6, *6/*28 and irinotecan-related neutropenia in Asian cancer patients receiving irinotecan regimen chemotherapy.
Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.
g-C3N4, as a typical metal-free catalyst for water splitting, has attracted special attention. The structural and electronic properties of water adsorption on g-C3N4 play a key role in understanding the water splitting mechanism at the atomic level. The properties of a single g-C3N4 sheet and the water adsorption on a single g-C3N4 sheet were thoroughly explored based on density functional theory (DFT) calculations. The results show that water adsorption on one side of the single g-C3N4 sheet will lead the initial flat structure to change to a buckle one, while water molecule adsorption on both sides of g-C3N4 will not disturb the flat structure. The flat g-C3N4 is an indirect semiconductor, and interestingly the band structure of g-C3N4 changes from an indirect to a direct one during the flat structure transformation from flat to buckle because of the water adsorption. Water molecules prefer to adsorb around the intrinsic vacancy of the single g-C3N4 sheet at low coverage, and further adsorbed water molecules stay around the intrinsic vacancy. Water adsorption also affects the band edge position of g-C3N4 for water splitting. These results provide a deep insight into the structure and adsorption properties of g-C3N4 in the water environment, which will greatly help to design a new type of metal-free catalyst for water-splitting.
Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition that causes severe loss of bone mass in the vertebrae and long bones. We explored the effect and the possible underlying mechanism of the extracts of Astragalus (AE) on the tooth alveolar bone rebuilding progress of postmenopausal osteoporosis of PMO animal models.
Coxsackievirus A16 (CA16) is one of the main causative pathogens of hand, foot and mouth disease (HFMD). Viral replication typically results in host cell apoptosis. Although CA16 infection has been reported to induce apoptosis in the human rhabdomyosarcoma (RD) cell line, it remains unclear whether CA16 induces apoptosis in diverse cell types, especially neural cells which have important clinical significance. In the current study, CA16 infection was found to induce similar apoptotic responses in both neural cells and non-neural cells in vitro, including nuclear fragmentation, DNA fragmentation and phosphatidylserine translocation. CA16 generally is not known to lead to serious neurological symptoms in vivo. In order to further clarify the correlation between clinical symptoms and cell apoptosis, two CA16 strains from patients with different clinical features were investigated. The results showed that both CA16 strains with or without neurological symptoms in infected patients led to neural and muscle cell apoptosis. Furthermore, mechanistic studies showed that CA16 infection induced apoptosis through the same mechanism in both neural and non-neural cells, namely via activation of both the mitochondrial (intrinsic) pathway-related caspase 9 protein and the Fas death receptor (extrinsic) pathway-related caspase 8 protein. Understanding the mechanisms by which CA16 infection induces apoptosis in both neural and non-neural cells will facilitate a better understanding of CA16 pathogenesis.
Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension.
Osteosarcoma is one of the most common primary bone malignancies. Although there is a significant improvement of survival on osteosarcoma patients in the past decades, treatment of osteosarcoma is still unsatisfactory for the development of pulmonary metastasis. The potential prognostic value of p16(INK4a) in osteosarcoma has been investigated, however, the results from different studies were somewhat controversial. To elucidate whether p16(INK4a) is indeed a prognostic factor of osteosarcoma, we conducted a meta-analysis of the published literatures to provide a comprehensive evaluation of the significance of p16(INK4a) expression in patients with osteosarcoma. Eight studies with a total of 354 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) was calculated to evaluate the effect of p16(INK4a) expression on overall survival. Meta-analysis showed that patients with high p16(INK4a) expression were significantly associated with favourable overall survival when compared to their counterparts with low or undetectable p16(INK4a) expression (OR = 0.270, 95% CI 0.162-0.451, P < 0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. In conclusion, the results from this meta-analysis highlight that p16(INK4a) is an effective biomarker of survival in patients with osteosarcoma.
Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration.
Aphids, the destructive insect pests in the agriculture, horticulture and forestry, are capable of reproducing asexually and sexually upon environmental change. However, the molecular basis of aphid reproductive mode switch remains an enigma. Here we report a comparative analysis of differential gene expression profiling among parthenogenetic females, gynoparae and sexual females of the cotton aphid Aphis gossypii, using the RNA-seq approach with next-generation sequencing platforms, followed by RT-qPCR. At the cutoff criteria of fold change ?2 and P<0.01, we identified 741 up- and 879 down-regulated genes in gynoparae versus parthenogenetic females, 2,101 up- and 2,210 down-regulated genes in sexual females compared to gynoparae, and 1,614 up- and 2,238 down-regulated genes in sexual females relative to parthenogenetic females. Gene ontology category and KEGG pathway analysis suggest the involvement of differentially expressed genes in multiple cellular signaling pathways into the reproductive mode transition, including phototransduction, cuticle composition, progesterone-mediated oocyte maturation and endocrine regulation. This study forms a basis for deciphering the molecular mechanisms underlying the shift from asexual to sexual reproduction in the cotton aphid. It also provides valuable resources for future studies on this host-alternating aphid species, and the insight into the understanding of reproductive mode plasticity in different aphid species.
Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.
Context: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-?-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumor invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC. Objective: The objective of the investigation was to study the role of LAMC2 in ATC tumorigenesis. Design: LAMC2 expression was evaluated by RT-PCR, Western blotting, and immunohistochemistry in tumor specimens, adjacent noncancerous tissues, and cell lines. The short hairpin RNA (shRNA) approach was used to investigate the effect of LAMC2 knockdown on the tumorigenesis of ATC. Results: LAMC2 was highly expressed in ATC samples and cell lines compared with normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed the migration, invasion, and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered the expression of genes associated with migration, invasion, proliferation, and survival. Immunoprecipitation studies showed that LAMC2 bound to epidermal growth factor receptor (EGFR) in the ATC cells. Silencing LAMC2 partially blocked epidermal growth factor-mediated activation of EGFR and its downstream pathway. Interestingly, cetuximab (an EGFR blocking antibody) or EGFR small interfering RNA additively enhanced the antiproliferative activity of the LAMC2 knockdown ATC cells compared with the control cells. Conclusions: To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration, invasion, and EGFR signaling in ATC cells, suggesting that LAMC2 may be a potential therapeutic target for the treatment of ATC.
To assess the association between a 5T polymorphism in intron 8 of cystic fibrosis transmembrane conductance regulator (CFTR) gene and congenital bilateral absence of vas deferens (CBAVD) in Han Chinese males.
A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta- analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity = 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.
OBJECTIVE To investigate the expression of gap junction protein Cx43 in the cardiac muscle of spontaneous hypertensive rat and the effects of various antagonists against renin angiotensin aldosterone system (RAAS) on Cx43 expression. METHODS 70 spontaneous hypertensive rats of 8-week age, 200-gram weight were separated into 7 groups, as hypertension, ramipril, telmisartan, eplerenone, ramipril + telmisartan, telmisartan + eplerenone, and ramipril+eplerenone treatment group. Another 10 healthy Wistar rats of the same age and weight were used as control group. All the rats were given intragastric administration at 8 a. m. every morning, and measured arteria caudilis pressure at 0, 4 and 8 week, respectively. 8 weeks later, all the rats were sacrificed, and the hearts were taken to measure the weight of left ventricle and the ratio of left ventricle to body weight. Myocardial fibrosis was observed by H&E staining of paraffin embedded sections, and Cx43 expression was examined by RT-PCR and western blot.
T-cell acute lymphoblastic leukemias (T-ALLs) are clonal lymphoid malignancies with a poor prognosis, and still a lack of effective treatment. Here we examined the interactions between the mammalian target of rapamycin (mTOR) inhibitor rapamycin and idarubicin (IDA) in a series of human T-ALL cell lines Molt-4, Jurkat, CCRF-CEM and CEM/C1. Co-exposure of cells to rapamycin and IDA synergistically induced T-ALL cell growth inhibition and apoptosis mediated by caspase activation via the intrinsic mitochondrial pathway and extrinsic pathway. Combined treatment with rapamycin and IDA down-regulated Bcl-2 and Mcl-1, and inhibited the activation of phosphoinositide 3-kinase (PI3K)/mTOR and extracellular signal-related kinase (ERK). They also played synergistic pro-apoptotic roles in the drug-resistant microenvironment simulated by mesenchymal stem cells (MSCs) as a feeder layer. In addition, MSCs protected T-ALL cells from IDA cytotoxicity by up-regulating ERK phosphorylation, while rapamycin efficiently reversed this protective effect. Taken together, we confirm the synergistic antitumor effects of rapamycin and IDA, and provide an insight into the potential future clinical applications of combined rapamycin-IDA regimens for treating T-cell malignancies.
A novel glucose oxidase/chitosan/?-zirconium phosphate (GOD/chitosan/?-ZrP) ternary biocomposite was prepared by co-intercalating glucose oxidase (GOD) and chitosan into the interlayers of ?-zirconium phosphate (?-ZrP) via a delamination-reassembly procedure. The results of X-ray diffraction, infrared spectroscopy, circular dichroism, and ultraviolet spectrum characterizations indicated not only the layered and hybrid structure of the GOD/chitosan/?-ZrP ternary biocomposite but also the recovered activity of the intercalated GOD improved by the co-intercalated chitosan. By depositing the GOD/chitosan/?-ZrP biocomposite film onto a glassy carbon electrode, the direct electrochemistry of the intercalated GOD was achieved with a fast electron transfer rate constant, ks, of 7.48±3.52s(-1). Moreover, this GOD/chitosan/?-ZrP biocomposite modified electrode exhibited a sensitive response to glucose in the linear range of 0.25-8.0mM (R=0.9994, n=14), with a determination limit of 0.076mM.
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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.